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Invasive Fungal Disease in Humans: Are We Aware of the Real Impact?

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Invasive Fungal Disease in Humans: Are We Aware of the Real Impact? PERSPECTIVE Mem Inst Oswaldo Cruz, Rio de Janeiro, Vol. 115: e200430, 2020 1|9 Invasive fungal disease in humans: are we aware of the real impact? Carolina Firacative1/+ 1Universidad del Rosario, School of Medicine and Health Sciences, Studies in Translational Microbiology and Emerging Diseases (MICROS) Research Group, Bogota, Colombia Despite the medical advances and interventions to improve the quality of life of those in intensive care, people with cancer or severely immunocompromised or other susceptible hosts, invasive fungal diseases (IFD) remain severe and underappreciated causes of illness and death worldwide. Therefore, IFD continue to be a public health threat and a major hindrance to the success of otherwise life-saving treatments and procedures. Globally, hundreds of thousands of people are affected every year with Candida albicans, Aspergillus fumigatus, Cryptococcus neoformans, Pneumocystis jirovecii, endemic dimorphic fungi and Mucormycetes, the most common fungal species causing invasive diseases in humans. These infections result in morbidity and mortality rates that are unacceptable and represent a considerable socioeconomic burden. Raising the general awareness of the significance and impact of IFD in human health, in both the hospital and the community, is hence critical to understand the scale of the problem and to raise interest to help fighting these devastating diseases. Key words: fungi - immunocompromised host - invasive fungal disease - risk factors It is estimated that the fungal kingdom has six million of fungi in their natural habitat, are also important ele- species widely distributed in the environment.(1) Among ments that influence on the incidence and prevalence of these, several hundred species of both yeasts and molds fungal disease across the world.(6) can affect humans in several ways. The direct ingestion In this perspective article, the main risk factors of of poisonous mushrooms causes mycetismus, which can people to develop IFD are summarised, to aid recognis- result in gastrointestinal tract disorders or even death. In ing the impact of fungi on human health, an issue often cases of mycotoxicosis, humans can be also poisoned by underestimated and underappreciated. Considering that the ingestion of food contaminated with fungal toxins IFD are often disregarded during routine hospital care, (mycotoxins), which affect the liver, kidneys and other it is very important to emphasise to microbiologists, di- vital organs.(2) Lastly, causing infection, fungi can be ei- agnostic laboratory staff and clinicians, that not only the ther primary or opportunistic pathogens of humans and number but the diversity of patients at-risk for IFD are the disease is called mycosis. Ranging from superficial continuously rising, with mortality rates than remain un- infections of the hair, skin, nails or mucosal surfaces, acceptably high.(3) Additionally, most fungal infections which are usually benign, and other ailments includ- are not reportable diseases, thus reliable information on ing allergies, fungi can also cause invasive infections local and global prevalence is not available. This review of internal organs that are progressive and lethal if not recalls the updated definition of IFD, collates recent epi- diagnosed and specifically treated.(3,4) To cause invasive demiological data and describes, in order of frequency, disease in humans, however, fungi must meet four crite- the most susceptible groups of people to acquire an ria: (i) the ability to grow at or above mammalian body IFD, namely those who undergo medical interventions, temperature; (ii) the ability to reach internal tissues by people with immunosuppression induced either by the penetrating or evading host barriers; (iii) the ability to treatment of an associated illnesses or by an underlying lyse tissues and absorb their components; and (iv) the disease, people with bacterial or viral co-infections and ability to evade host immune defences.(5) As warm- immunocompetent individuals who acquire an IFD by blooded animals with a highly sophisticated immune environmental exposure. system, humans are naturally resistant to most invasive Invasive fungal diseases fungal diseases (IFD). As such, most cases of invasive disease occur in patients with an underlying serious ill- According to standard criteria, an invasive or sys- ness or condition. Moreover, advances in medical care temic fungal disease is proven when tissue damage due and life-saving treatments, which may lead to an im- to fungal elements is observed by histopathologic ex- paired immune function, have increased the number of amination and/or when the aetiologic agent is isolated susceptible patients or people at-risk for fungal infec- by culture from clinical sterile samples such as blood, tions.(5) Lastly, socioeconomic and geoecological char- tissue or cerebrospinal fluid.(7) Infection can be initiated acteristics, including the exposure to a high inoculum by invasion of fungal microbiota into the mucosa, by the inhalation of fungal spores from the environment or by direct inoculation, which lead to colonisation and dis- semination. As clinical manifestations of IFD are not doi: 10.1590/0074-02760200430 specific and the severity of the disease depends on the + Corresponding author: [email protected] https://orcid.org/0000-0001-7547-5172 host’s defences and immune response, a high degree of Received 21 August 2020 suspicion is needed for the early diagnosis and optimal Accepted 24 September 2020 management of these infections.(8) online | memorias.ioc.fiocruz.br 2|9 Carolina Firacative IFD are an emerging problem worldwide, are gener- a physical barrier intrinsically resistant to the host im- ally very difficult to cure and the associated mortality re- mune system and other environmental perturbations.(14) mains very high depending on the pathogen and patient The formation of biofilms additionally leads to upregu- population. Recent studies have estimated that globally, lation of antifungal-resistance mechanisms, as well as fungal infections kill more than 1.5 million people per the development of complex regulatory processes that year, which is similar to the mortality due to tuberculosis favour even higher levels of antifungal resistance, most and about three-times more than malaria.(6) However, the notably to azoles and polyenes.(15) Directly related with true burden of IFD is probably miscalculated because of medical interventions, nosocomial candidaemia is as- the absence or availability of reliable, sensitive and uni- sociated with prolonged stays in hospital and intensive versal diagnostic methods and because fungal infections care units, parenteral nutrition, as well as with improved are usually hindered by other diseases. Furthermore, survival of premature infants.(11) Despite the broad use when cases of fungal diseases are identified by a health of antifungal prophylaxis, mostly fluconazole, which provider, hospital or laboratory, they are not mandatory has shown to reduce the incidence of invasive candidia- to be reported to public health departments; hence, most sis in patients who are at highest risk, almost 750,000 countries lack surveillance systems for IFD. cases of this mycosis are estimated to occur yearly in Among at-risk and immunocompromised patients, the world.(6,12) Although C. albicans is the global leading Candida albicans, Aspergillus fumigatus, Cryptococcus agent of candidaemia and other forms of invasive candi- neoformans, Pneumocystis jirovecii, endemic dimorphic diasis, accounting for about half the amount of cases, the fungi and Mucormycetes remain the main fungal patho- frequency of non-albicans species, mainly C. glabrata, gens responsible for most cases of serious fungal diseases C. parapsilosis, C. tropicalis and C. krusei is increasing, in the world (Tables I, II, Figure).(5,6,9,10) While the ability which is of concern when selecting empiric antifungal of these fungi to cause disease depends on their virulence therapy, as non-albicans species have reduced suscepti- factors and pathogenic capacity, as well as on the interac- bility or are intrinsically resistance to azoles.(11) tions with the host and adaptation to different environ- Much less frequently, in both immunocompetent ments, the outcome of the infections is influenced by and immunocompromised individuals, fungi, includ- various others factors. The patients’ underlying medical ing Candida spp., can be directly inoculated through condition, the time for diagnosis, the choice of therapy, neurosurgical procedures and contaminated devices or especially when fighting strains or species that are resis- drug preparations. An unprecedented outbreak of fungal tant to antifungal drugs, the capacity to achieve prompt meningitis, for instance, was associated with parenteral and effective source control, and the adverse effects of injections of corticosteroids contaminated with A. fu- antifungal drugs alone or concomitantly administered migatus and Exserohilum rostratum, both environmen- with other drugs, are factors that significantly contribute tal molds.(16,17) Another saprophyte mold, Sarocladium to IFD prognosis.(5) Thus, identifying susceptible patients kiliense, was isolated from several fungaemia cases as- or those who are clinically suspected of having a fungal sociated with the administration of contaminated antin- infection, along with an early empiric therapy or prophy- ausea medication among oncology patients.(18,19) laxis, are of paramount importance to decrease mortality Treatment-induced
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